Recognition sites for a variety of psychotherapeutic drugs have been identified in the mammalian central nervous system. Several of these binding sites, including those for benzodiazepines, opiates, and various neuroleptics have subsequently been shown to be true pharmacological receptors in that the binding of drug to its respective recognition site is a necessary (and many times sufficient) requirement for drug action. Over the past several years we have attempted to identify recognition sites for other common psychotropic drugs including tricyclic antidepressants and the psychomotor stimulants, amphetamine and methylphenidate. In each case relatively high affinity, saturable, and stereospecific binding sites have been delineated; and for amphetamine and methylphenidate relatively good correlations have been observed between the affinities of a series of analogues in vitro and at least some of the pharmacological properties of these agents. Tricyclic antidepressants including imipramine and desipramine, also bind to distinct recognition sites that are functionally and structurally associated with the presynaptic uptake sites for serotonin and norepinephrine respectively. Thus, radiolableled antidepressants have been useful probes in studying the mechanisms of neurotransmitter uptake in both central and peripheral tissues, and under a variety of clinical conditions. Studies on elucidating the possible physiological significance of these binding sites as well as their relationship to pathophysiological mechanisms of neuropsychiatric disease are in progress.